S273: LONG-TERM ERYTHROID RESPONSE DATA FROM PATIENTS (PTS) WITH NON-TRANSFUSION-DEPENDENT ΒETA-THALASSEMIA (NTDT) RECEIVING LUSPATERCEPT IN THE BEYOND TRIAL
Authors: Ali T. Taher, Vip Viprakasit, Maria Domenica Cappellini, Antonio Giulio Piga, John B. Porter, Thomas D. Coates, Khaled M. Musallam, Gian Luca Forni, Jeevan K. Shetty, Marija Bosilkovska Weisskopf, Richard Wei, Wen-Ling Kuo, Antonis Kattamis
Journal: HemaSphere (2023)

Background: Pts with NTDT can develop serious clinical complications due to untreated anemia. While there are no approved treatments (txs) for NTDT-associated anemia, luspatercept tx was shown to decrease transfusion burden and durably increase hemoglobin (Hb) levels in transfusion-dependent β-thalassemia (Cappellini MD, et al. N Engl J Med 2020;382:1219–1231; Taher AT, et al. HemaSphere 2021;5[suppl 2]. Abstract S101). Aims: To report long-term efficacy data from pts with NTDT receiving luspatercept in the BEYOND trial (NCT03342404). Methods: Eligible pts (N=145) had NTDT or HbE/β-thalassemia (defined as 0–5 RBC units transfused in the 24 wk prior to randomization) and Hb levels ≤10 g/dL. Pts were randomized to receive luspatercept (1.0–1.25 mg/kg) or placebo subcutaneously for ≥48 wk. Pt assignment at randomization determined assessment groups: pts randomized to luspatercept were assessed on tx, while pts receiving placebo were assessed up to discontinuation or crossover to luspatercept. Mean change in Hb from baseline was assessed for continuous 12-wk intervals up to wk 144. Erythroid response was defined as mean change in Hb from baseline of ≥1 g/dL, assessed over rolling 12-wk intervals. The incidence of RBC transfusion events and units transfused was assessed. Results: As of Sep 22, 2021, 83 (86.5%) and 16 (32.7%) pts in the luspatercept and placebo arms completed ≥96 wk of tx, respectively; 72 (75.0%) pts in the luspatercept arm completed ≥120 wk of tx. In the luspatercept and placebo arms, the median (range) duration of tx was 150.1 (15.0–185.4) wk and 61.1 (3.0–138.0) wk, respectively. A median (range) of 42.0 (3.0–61.0) and 20.0 (1.0–46.0) doses were received per pt in the luspatercept and placebo arms, respectively. In the luspatercept arm, mean (standard error) Hb change from baseline was 1.28 (0.069) g/dL during wk 1–12 and 1.48 (0.078) g/dL during wk 13–24; the increase was maintained in pts remaining on study across all time points. Hb level improvements from baseline were nominally significant versus placebo at 12-wk intervals assessed up to wk 96 (Figure). The mean (standard deviation [SD]) change from baseline in liver iron content at wk 48 was −0.24 (1.51) mg/g dry weight with luspatercept (n=85). The proportion of pts who had an erythroid response during any 12-wk interval increased from 91.7% (88/96 pts) at the primary data cutoff date (Sep 14, 2020) to 93.8% (90/96 pts) at the current data cutoff date. The proportion of luspatercept arm responders with ≥1 12-wk rolling response increased from 35.2% (31/88 pts) to 61.1% (55/90 pts) between the primary and current data cutoff dates; the mean (SD) total duration of erythroid response in pts with ≥1 12-wk rolling response also increased, from 611.1 (243.3) to 873.1 (363.4) days. A smaller proportion of pts in the luspatercept than the placebo arm (10.4% [10/96 pts] vs 32.7% [16/49 pts]) received ≥2 RBC transfusions during wk 1–96. The mean number of RBC units transfused (0.7 vs 2.2) and transfusion events (0.4 vs 1.3) per pt was lower in the luspatercept than the placebo arm over the same period. The mean number of transfusion units and events per pt remained stable in the luspatercept arm (0.2 units and 0.2 events) during wk 97–144. Summary/Conclusion: Hb levels were sustained and significantly improved in pts with NTDT receiving long-term luspatercept tx. Erythroid response duration was improved with an additional year of luspatercept tx. Few pts required RBC transfusions, with the cumulative incidence of transfusions remaining low and relatively stable through 144 wk.Keywords: Hemoglobin, Clinical trial, Erythroid, beta thalassemia